2 year old girl with 2 year old girl with tetanytetanyKatie Stanley, MDKatie Stanley, MDFebruary 16, 2012February 16, 2012

History of Present IllnessHistory of Present Illness2 2 yoyo previously healthy female in usual state of previously healthy female in usual state of health until morning of admissionhealth until morning of admissionNoted to be holding her hands in abnormal Noted to be holding her hands in abnormal position, not able to grip objects with her fingersposition, not able to grip objects with her fingersAlso having difficulty walkingAlso having difficulty walking

Feet in flexed positionFeet in flexed position

c/o foot painc/o foot painHas been otherwise wellHas been otherwise wellVegan dietVegan dietPresented to ER where found to have Ca 5.3Presented to ER where found to have Ca 5.3

Past, Family, and Social HistoryPast, Family, and Social HistoryPast medical historyPast medical history

Born at 37Born at 37--38 wks, uncomplicated 38 wks, uncomplicated

Healthy, has not seen pediatrician since 4 Healthy, has not seen pediatrician since 4 mosmos, no , no immunizations after that timeimmunizations after that time

Development on track with older sister at same age (walked at Development on track with older sister at same age (walked at 10 10 mosmos, talking), talking)

No medications except occasional herbal supplementsNo medications except occasional herbal supplementsFamily HistoryFamily History

No rickets, calcium disorders, renal disorders, kidney stonesNo rickets, calcium disorders, renal disorders, kidney stones

Social HistorySocial History

Lives in Hyde Park with both parents, 4 Lives in Hyde Park with both parents, 4 yoyo sister, mother is sister, mother is pregnant with third childpregnant with third child

Dietary HistoryDietary HistoryExclusively breast fed until 10 Exclusively breast fed until 10 mosmos of ageof ageTable foods added at 10 Table foods added at 10 mosmos, weaned off breast , weaned off breast milk shortly after 1 milk shortly after 1 yoyo ageageEats primarily fruits and Eats primarily fruits and nonfortifiednonfortified cerealscerealsHas rice milk only on her cereal, no other vegan Has rice milk only on her cereal, no other vegan dairy productsdairy productsWas on TriWas on Tri--vivi--sol for some period of time in sol for some period of time in infancy but no supplementation sinceinfancy but no supplementation sincePlays outside when it is warm, but had 1 hr or Plays outside when it is warm, but had 1 hr or less of sun exposure daily over the prior several less of sun exposure daily over the prior several monthsmonths

Review of SystemsReview of SystemsConstitutional: Positive for irritability. Constitutional: Positive for irritability. HENT: Negative. HENT: Negative. Eyes: Negative. Eyes: Negative. Respiratory: Negative. Negative for Respiratory: Negative. Negative for stridorstridor. . Cardiovascular: Negative. Cardiovascular: Negative. Gastrointestinal: Negative. Gastrointestinal: Negative. Genitourinary: Negative. Genitourinary: Negative. Musculoskeletal: Positive for muscle cramping. Musculoskeletal: Positive for muscle cramping. Skin: Negative. Skin: Negative. Neurological: Neurological:

Spasms of hands and feetSpasms of hands and feet

No seizures or mental status changesNo seizures or mental status changesHematological: Negative. Hematological: Negative. Psychiatric/Behavioral: Negative. Psychiatric/Behavioral: Negative.

Physical ExamPhysical ExamVitals: T37.8, P147, R 32, 111/54, SaO2 100% RA, Wt 11.9 kg (42%Vitals: T37.8, P147, R 32, 111/54, SaO2 100% RA, Wt 11.9 kg (42%))Constitutional: WellConstitutional: Well--developed and welldeveloped and well--nourished, NAD. nourished, NAD. HENT: HENT: FontanellesFontanelles closed. No bossing noted.closed. No bossing noted.Eyes: Conjunctivae are normal. PEERL.Eyes: Conjunctivae are normal. PEERL.Neck: Neck supple. No Neck: Neck supple. No thyromegalythyromegaly..Cardiovascular: Normal rate, regular rhythm, S1 normal and S2 noCardiovascular: Normal rate, regular rhythm, S1 normal and S2 normal. No rmal. No murmurs. No edema.murmurs. No edema.Pulmonary/Chest: Effort normal and breath sounds normal. Pulmonary/Chest: Effort normal and breath sounds normal. Abdominal: Soft. No distension. No tenderness. Abdominal: Soft. No distension. No tenderness. No HSMNo HSMMusculoskeletal: Normal range of motion. No widening of wrists. Musculoskeletal: Normal range of motion. No widening of wrists. No rachitic No rachitic rosary. At rosary. At b/lb/l hand the pts fingers are locked in extension with the thumbs hand the pts fingers are locked in extension with the thumbs adducted over the palms. She plays games on a cell phone but keeadducted over the palms. She plays games on a cell phone but keeps her ps her hands in the above described position.hands in the above described position.Neurological: She is alert, appropriate mental status. Negative Neurological: She is alert, appropriate mental status. Negative ChvostekChvostek sign.sign.

Diff Diff dxdx of of hypocalcemiahypocalcemiaHypoparathyoidismHypoparathyoidism

DiGeorgeDiGeorge

CaSRCaSR defectdefect

AutoimmuneAutoimmune

Other acquired, Other acquired, egeg postpost--surgicalsurgical

PTH resistancePTH resistance

HypomagnesemiaHypomagnesemia

HypovitaminosisHypovitaminosis DD

NutritionalNutritional

Renal diseaseRenal disease

Liver diseaseLiver disease

Defective vitamin D Defective vitamin D hydroxylationhydroxylation

Vitamin D resistanceVitamin D resistanceOtherOther

HyperphosphatemiaHyperphosphatemia

Citrated productsCitrated products

PancreatitisPancreatitis

Labs and StudiesLabs and Studies

CMP: Na 138, K 4.5, CMP: Na 138, K 4.5, ClCl 103, HCO3 19, 103, HCO3 19, BUN 5, Cr 0.3, BUN 5, Cr 0.3, GluGlu 104, 104, Ca 5.3Ca 5.3, , PO4 4.2PO4 4.2, , Mg 1.7, Prot 6.2, Alb 4.8, Mg 1.7, Prot 6.2, Alb 4.8, BiliBili 0.3, 0.3, AlkAlk PhosPhos 17961796, AST 40, ALT 13 , AST 40, ALT 13 Ionized calcium 2.32Ionized calcium 2.32PTH 309PTH 30925OH25OH--vitamin D <5vitamin D <51,25OH1,25OH--vitamin D 28vitamin D 28EKG EKG QTcQTc 432 (432 (nlnl<450) <450)

Chest xChest x--rayray

Patient Sample

Wrist xWrist x--rayray

Patient Sample

Initial ManagementInitial Management

Ca Ca gluconategluconate 1 g IV x 1 (~100 mg Ca 1 g IV x 1 (~100 mg Ca gluconategluconate/kg/dose)/kg/dose)CalcitriolCalcitriol 0.25 mcg IV x 10.25 mcg IV x 1Calcium carbonate 625 mg PO TID (63 mg Calcium carbonate 625 mg PO TID (63 mg elemental Ca/kg/day)elemental Ca/kg/day)Symptoms largely resolved after initial IV Symptoms largely resolved after initial IV calcium calcium gluconategluconate

Hospital CourseHospital CourseAdmitted to PICUAdmitted to PICURecommended Ca Recommended Ca gluconategluconate gttgtt but delay in but delay in starting for PICC placementstarting for PICC placementCa 6.1 ~ 6 hrs after receiving rider, before Ca 6.1 ~ 6 hrs after receiving rider, before starting starting gttgttCa Ca gluconategluconate gttgtt @ 150 mg/hr (~500 mg Ca @ 150 mg/hr (~500 mg Ca gluc/kg/24 hrs), gluc/kg/24 hrs), calcitriolcalcitriol and PO Ca and PO Ca carbcarb continuedcontinuedCa 7.1 4 hrs later, 7.6 10 hrs laterCa 7.1 4 hrs later, 7.6 10 hrs laterParents interested in Parents interested in ““naturalnatural”” supplementssupplements

WebsiteWebsite

FormulasFormulas

Calcium (Herbal) Calcium (Herbal) -- 100 Capsules100 Capsules$14.95 $14.95 Sale:Sale: $11.96$11.96 Save:Save: 20% off20% offActivity: Activity: Djehuty'sDjehuty's Calcium Phosphate Calcium Phosphate contains plants high in organic calcium that contains plants high in organic calcium that ensure and maintain proper nerve functioning ensure and maintain proper nerve functioning and bone and skeletal development. Calcium and bone and skeletal development. Calcium is the most abundant mineral in the human is the most abundant mineral in the human body. body.

Ingredients: COMFREY LEAVES, OAT Ingredients: COMFREY LEAVES, OAT STRAW, HORSETAIL, AND RED STRAW, HORSETAIL, AND RED RASPBERRY LEAVES. RASPBERRY LEAVES.

Vitamin D Vitamin D -- 100 Capsules100 Capsules$9.95 $9.95 Sale:Sale: $7.96$7.96 Save:Save: 20% off20% offActivity:Activity: Our Vitamin D formula consists of plants Our Vitamin D formula consists of plants that are high in organic Vitamin D which is an that are high in organic Vitamin D which is an essential nutrient that is necessary for the essential nutrient that is necessary for the absorption and utilization of calcium and absorption and utilization of calcium and phosphorus by the intestinal tract and for the normal phosphorus by the intestinal tract and for the normal growth and development of the bones and teeth. growth and development of the bones and teeth. Helps to maintain bone health!Helps to maintain bone health!

Ingredients:Ingredients: ALFALFA, RED RASPBERRY ALFALFA, RED RASPBERRY LEAVES, MULLEIN LEAVES, EYEBRIGHT, LEAVES, MULLEIN LEAVES, EYEBRIGHT, FENUGREEK SEED, OAT STRAW, THYME, FENUGREEK SEED, OAT STRAW, THYME, ROSE HIP SEED, AND SARSAPARILLA.ROSE HIP SEED, AND SARSAPARILLA.

Hospital Course continuedHospital Course continued

Ca Ca gttgtt heldheld--> Ca 7.0 4 hrs later> Ca 7.0 4 hrs laterCa 6 hrs later 6.9Ca 6 hrs later 6.9--> Ca > Ca glucgluc 1 g IV1 g IVStarted on Started on ergocalciferolergocalciferol 10,000 units daily10,000 units dailySerum Ca 7.5Serum Ca 7.5--8.1 for next 36 hrs8.1 for next 36 hrsDischarged on ergo 4000 units, Discharged on ergo 4000 units, calcitriolcalcitriol 0.25 mcg bid, Ca carbonate 625 mg PO 0.25 mcg bid, Ca carbonate 625 mg PO TIDTIDCa 4 d after discharge 8.7Ca 4 d after discharge 8.7--> > calcitriolcalcitriol reduced to reduced to qdqd

Vitamin D Deficiency and Vegan Vitamin D Deficiency and Vegan DietDiet

24 children presenting to CHOP 197424 children presenting to CHOP 1974--1978 with rickets1978 with rickets

11/24 on vegan diet11/24 on vegan diet

Only 2 received MVI>3 Only 2 received MVI>3 mosmos

Sunlight, maternal contributionSunlight, maternal contribution

Lack of biochemical and xLack of biochemical and x--ray correlationray correlationStudy of Black Hebrew community in Israel 1979Study of Black Hebrew community in Israel 1979--19801980

9/25 admitted to hospital had rickets 9/25 admitted to hospital had rickets

Well childrenWell children20 Rastafarian children on vegan diet20 Rastafarian children on vegan diet

7 had rickets7 had rickets

Children with rickets had lower Children with rickets had lower HgbHgb than children without ricketsthan children without ricketsPostPost--menopausal Vietnamese vegan women had lower menopausal Vietnamese vegan women had lower 25OHD levels but no difference in BMD or fracture rate 25OHD levels but no difference in BMD or fracture rate over 2 years from omnivoresover 2 years from omnivores

Herbal Ca and Vitamin DHerbal Ca and Vitamin D-- Effective Effective and Safe?and Safe?

Plant based calciumPlant based calcium

2011 study evaluating change in BMD over 1 2011 study evaluating change in BMD over 1 year in women >40 with regimen including year in women >40 with regimen including algae derived calcium algae derived calcium

AlfalfaAlfalfa

1920 IU 1920 IU ergocalciferolergocalciferol/kg/kg

Seeds can cause lupusSeeds can cause lupus--like syndromelike syndromeHorsetailHorsetail

Thiamine deficiencyThiamine deficiency

Multiple case reports of hepatic Multiple case reports of hepatic venoveno-- occlusive disease associated with comfrey occlusive disease associated with comfrey ingestioningestionToxicity related to Toxicity related to pyrrolizidinepyrrolizidine alkaloidsalkaloidsCarcinogenicity in ratsCarcinogenicity in rats

Dose responseDose responseMutagenicityMutagenicity in ratsin rats

Journal of Toxicology and Environmental Health, PartB: Critical ReviewsMetabolism, Genotoxicity, annd Carcinogenicity ofComfreyNan Mei a , Lei Guo b , Peter P. Fu b , James C. Fuscoe c , Yang Luan d & Tao Chen a

ReferencesReferencesBachrachBachrach SB, Fisher JF, and Parks JS. An outbreak of vitamin D deficienSB, Fisher JF, and Parks JS. An outbreak of vitamin D deficiency rickets in cy rickets in a susceptible population. a susceptible population. PediatricsPediatrics. 1979: 871. 1979: 871--876.876.HoHo--Pham LT, Vu BQ, Lai TQ, Nguyen ND, and Nguyen TV. VegetarianismPham LT, Vu BQ, Lai TQ, Nguyen ND, and Nguyen TV. Vegetarianism, bone , bone loss, fracture, and vitamin D: a longitudinal study in Asian vegloss, fracture, and vitamin D: a longitudinal study in Asian vegans and nonans and non--vegans. vegans. European Journal of Clinical NutritionEuropean Journal of Clinical Nutrition. 2012: 75. 2012: 75--82.82.Horst RL, Reinhardt TA, Horst RL, Reinhardt TA, RusselRussel JR, Napoli JL. The isolation and identification of JR, Napoli JL. The isolation and identification of vitamin D2 and vitamin D3 from vitamin D2 and vitamin D3 from MedicagoMedicago sativa sativa (alfalfa plant). (alfalfa plant). Archives of Archives of Biochemistry and BiophysicsBiochemistry and Biophysics. 1984: 67. 1984: 67--71.71.James JA, Clark C, and Ward PS. Screening Rastafarian children James JA, Clark C, and Ward PS. Screening Rastafarian children for nutritional for nutritional rickets. rickets. British Medical JournalBritish Medical Journal.1985: 899.1985: 899--900.900.KaatsKaats GR, GR, PreussPreuss HG, Croft HA, Keith SC, and Keith PL. A comparative HG, Croft HA, Keith SC, and Keith PL. A comparative effectiveness study of bone density changes in women over 40 foleffectiveness study of bone density changes in women over 40 following three bone lowing three bone health plans containing variations of the same novel planthealth plans containing variations of the same novel plant--sourced calcium. sourced calcium. IntInt J. J. Med Sci.Med Sci. 2011: 1802011: 180--191.191.Mei N, Mei N, GuoGuo L, Fu PF, L, Fu PF, FuscoeFuscoe JC, Luan Y, and Chen T. Metabolism, JC, Luan Y, and Chen T. Metabolism, genotoxicitygenotoxicity, , carcinogenicity of comfrey. carcinogenicity of comfrey. Journal of Toxicology and Environmental HealthJournal of Toxicology and Environmental Health. 2010: . 2010: 509509--526.526.Shinwell ED and Shinwell ED and GorodischerGorodischer R. Totally vegetarian diets and infant nutrition. R. Totally vegetarian diets and infant nutrition. Pediatrics. Pediatrics. 1982: 5821982: 582--586.586.