Vitamin B-6 Dependency Syndromes

Updated: Nov 06, 2014
  • Author: Haritha Reddy Chelimilla, MD; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
  • Print
Overview

Background

B6 dependency syndromes are a group of metabolic disorders which respond to large doses of vitamin B6. Although rare, pyridoxine-dependent seizure (PDS) is a recognized cause of intractable seizures in neonates, psychomotor developmental delay, and, sometimes, death in untreated patients. [1, 2, 3, 4, 5, 6] Hunt et al first described PDS in 1954. [7, 1, 8] Since then, fewer than 100 cases have been reported worldwide. [1, 3] Later onset seizures due to pyridoxine deficiency have been reported. [1, 9] The 2 types of presentations are classic and atypical. The classic presentation consists of intractable seizures that appear within hours of birth and are resistant to conventional anticonvulsants. The seizures rapidly respond to administration of parenteral pyridoxine in doses greater than physiologic doses. [1] A trial of pyridoxine is recommended in all seizures that have no clear etiology and occur before the child is aged 18 months. [9] Atypicalformsinclude those with seizures only partly responsive to pyridoxine, referred to as pyridoxine responsive seizures, and those with late onset of seizures. [2] Despite treatment children can have intellectual deficits or developmental delays.

PDS is probably an underdiagnosed and underreported condition. All medical specialists should be aware of its existence and potentially favorable outcome. [1] Lifelong supplementation of pyridoxine is required. [1, 3] Despite treatment developmental handicaps especially in expressive language are common.

Vitamin B-6 (pyridoxine)

See the list below:

  • Pyridoxine is water-soluble.
  • Sources include meat, nuts, and whole-grain products (especially wheat).
  • Deficiency usually occurs in conjunction with inadequate intake of other B vitamins due to poor diet or malabsorption states.
  • Isolated pyridoxine dependency can occur during treatment with isoniazid, which is a pyridoxine antagonist.
  • Pyridoxine requirements are increased in the presence of other drugs, including penicillamine, contraceptive steroids, and hydralazine.
  • Clinical features of deficiency in young infants include abnormal CNS activity (eg, irritability, aggravated startle response, seizures) and GI distress (eg, distension, vomiting, diarrhea).
  • Other manifestations include anemia, peripheral neuropathy, and dermatitis.
  • Treatment consists of pyridoxine 5 mg intramuscularly followed by 0.5 mg per day orally for 2 weeks. Correct dietary deficiency.
  • Consider pyridoxine dependency in the differential diagnosis of neonatal seizures when other more common causes have been eliminated. Rapid treatment with pyridoxine, 100 mg intramuscularly, is recommended.

The recommended daily dietary intake for pyridoxine is as follows:

  • Infants aged 0-6 months - 0.25 mg/d
  • Infants aged 7-12 months - 0.45 mg/d
  • Children aged 1-3 years - 0.6-0.9 mg/d
  • Children aged 4-7 years - 0.8-1.3 mg/d
  • Boys aged 8-11 years - 1.1-1.6 mg/d
  • Boys aged 12-15 years - 1.4-2.1 mg/d
  • Boys aged 16-18 years - 1.5-2.2 mg/d
  • Girls aged 8-11 years - 1-1.5 mg/d
  • Girls aged 12-15 years - 1.2-1.8 mg/d
  • Girls aged 16-18 years - 1.1-1.6 mg/d
Next:

Pathophysiology

PDS is an autosomal recessive inborn disorder of metabolism. [1, 9, 10] Some studies suggest that, as well as seizure activity, the neurobehavioral phenotype of the defective gene in PDS may include cognitive and other neuropsychologic impairment. [8] Some suggest that PDS is possibly caused by a glutamic acid decarboxylase (GAD) abnormality; [11] however, genetic analysis of GAD in affected families has not revealed any defects in this gene. [12, 13]

Subsequent studies showed elevated pipecolic acid levels in the plasma and cerebrospinal fluid of affected patients and this led to the recognition of a defect in aaminoadipic semialdehyde (a-AASA) dehydrogenase (antiquitin) in the cerebral lysine degradation pathway, and mutations in the antiquitin gene (ALDH7A1) on chromosome 5q31. [26] These gene defects occur in almost all neonatal onset cases of VB6 dependent seizures,and are also found in some, but not all, late-onset cases. [27] Pipecolic acid and a-AASA have become useful biomarkers for the diagnosis of VB6 dependency.Pipecolic acid acts as a modulator of GABA

Previous
Next:

Epidemiology

Frequency

United States

The frequency of PDS in the United States is unknown. Fewer than 100 cases have been reported in the literature; thus, the full range of symptomatology is unknown. [8] It has an estimated incidence of up to 1:20,000 live births. [28]

International

Burd et al reports prevalence data of 1 per 20,000-100,000 live births. [8] Data from the United Kingdom suggest a very low prevalence. A birth incidence of 1 in 783,000 and a point of prevalence of 1 in 687,000 (for definite and probable cases in children < 16 y) have been reported from the United Kingdom and the Republic of Ireland in 1999. [1, 8] In the Netherlands, birth incidence has been reported as 1:396,000 for definite and probable cases of PDS. [14]

Mortality/Morbidity

The literature has not reported mortality and morbidity rates.

Race

No particular race has been identified as more or less susceptible to the condition. Studies have mostly come from the United Kingdom because of misdiagnosis in less developed countries. In 2001, Gupta et al reported that PDS is underdiagnosed and underreported in India. [1]

Sex

The literature has not identified sex differences in susceptibility to PDS.

Age

Most reported cases have been in infants or young children. [1, 2, 9, 3] Outcomes of PDS in older children have rarely been reported.

Previous