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Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults.
Isr Med Assoc J. 2003 Dec; 5(12):868-72.IM

Abstract

BACKGROUND

Transcobalamin II is a serum transport protein for vitamin B12. Small variations in TC-II affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B12 deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

OBJECTIVES

To study 23 members of a four-generation family with hereditary vitamin B12 deficiency and neurologic disorders.

METHODS

Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

RESULTS

Partial TC-II deficiency was found in 19 subjects. Apo TC-II (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B12) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B12 injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

CONCLUSIONS

We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances--despite normal serum vitamin B12 levels. Low serum UBBC and apo TC-II should confirm the diagnosis. Early vitamin B12 therapy may prevent irreversible neurologic damage.

Authors+Show Affiliations

Department of Medicine C, Rabin Medical Center (Beilinson Campus), Petah Tiqva, Israel. teplit@zahav.net.ilNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14689755

Citation

Teplitsky, Valery, et al. "Hereditary Partial Transcobalamin II Deficiency With Neurologic, Mental and Hematologic Abnormalities in Children and Adults." The Israel Medical Association Journal : IMAJ, vol. 5, no. 12, 2003, pp. 868-72.
Teplitsky V, Huminer D, Zoldan J, et al. Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults. Isr Med Assoc J. 2003;5(12):868-72.
Teplitsky, V., Huminer, D., Zoldan, J., Pitlik, S., Shohat, M., & Mittelman, M. (2003). Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults. The Israel Medical Association Journal : IMAJ, 5(12), 868-72.
Teplitsky V, et al. Hereditary Partial Transcobalamin II Deficiency With Neurologic, Mental and Hematologic Abnormalities in Children and Adults. Isr Med Assoc J. 2003;5(12):868-72. PubMed PMID: 14689755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults. AU - Teplitsky,Valery, AU - Huminer,David, AU - Zoldan,Joseph, AU - Pitlik,Silvio, AU - Shohat,Mordechai, AU - Mittelman,Moshe, PY - 2003/12/24/pubmed PY - 2004/1/7/medline PY - 2003/12/24/entrez SP - 868 EP - 72 JF - The Israel Medical Association journal : IMAJ JO - Isr. Med. Assoc. J. VL - 5 IS - 12 N2 - BACKGROUND: Transcobalamin II is a serum transport protein for vitamin B12. Small variations in TC-II affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B12 deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes. OBJECTIVES: To study 23 members of a four-generation family with hereditary vitamin B12 deficiency and neurologic disorders. METHODS: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members. RESULTS: Partial TC-II deficiency was found in 19 subjects. Apo TC-II (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B12) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B12 injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency. CONCLUSIONS: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances--despite normal serum vitamin B12 levels. Low serum UBBC and apo TC-II should confirm the diagnosis. Early vitamin B12 therapy may prevent irreversible neurologic damage. SN - 1565-1088 UR - https://www.unboundmedicine.com/medline/citation/14689755/Hereditary_partial_transcobalamin_II_deficiency_with_neurologic_mental_and_hematologic_abnormalities_in_children_and_adults_ L2 - http://www.ima.org.il/IMAJ/ViewArticle.aspx?year=2003&month=12&page=868 DB - PRIME DP - Unbound Medicine ER -