[email protected] (受疫情影响,东南亚目前只开放曼谷诊所)
全周 (9AM - 5PM)


Extra info thumb
  • 总部: 泰国曼谷市巴吞汪区仑披尼分区 普勒吉路齐隆巷5号.
  • [email protected]


Alternative titles; symbolsLIPOYLTRANSFERASE 2 DEFICIENCY; LIPT2D▼ DescriptionNELABA is a severe autosomal recessive metabolic disorder characterized by onset at...

Alternative titles; symbols


▼ Description

NELABA is a severe autosomal recessive metabolic disorder characterized by onset at birth of progressive encephalopathy associated with increased serum lactate. Affected individuals have little or no psychomotor development and show brain abnormalities, including cerebral atrophy, cysts, and white matter abnormalities. Some patients die in infancy (summary by Habarou et al., 2017).

▼ Clinical Features

Habarou et al. (2017) reported 3 patients from 2 unrelated families with severe neonatal encephalopathy. Two sibs, born of unrelated German parents, died within the first 7 months of life without any psychomotor development. They presented at birth with severe hypotonia and/or respiratory insufficiency associated with lactic acidosis. They had some abnormal movements suspicious for epilepsy, and EEG showed reduced background activity and poor sleep-wake differentiation. Brain imaging was abnormal in both patients, showing enlarged ventricles, periventricular cystic changes, cortical cysts, and decreased gyration. The unrelated patient, born of nonconsanguineous parents, was alive at age 10 years. He presented at birth with hypotonia, spastic tetraparesis, and dystonia associated with increased serum lactate and lactate peak on MRS spectroscopy. He developed complex seizures at age 4, and EEG showed multiple abnormalities. He was severely disabled and could not sit, speak, or understand, was bed- and wheelchair-bound with no head control, and had microcephaly (-4 SD) and a feeding tube. Brain imaging showed progressive cerebral atrophy, white matter abnormalities, and delayed myelination. Treatment of this patient with lipoic acid supplementation did not result in any clinical improvement. Serum and urine studies of the 3 patients generally showed increased lactate, pyruvate, alanine, and 2-oxoglutarate, moderate hyperglycinemia, and decreased branched-chain amino acids. However, there was variability in the biochemical spectrum of abnormalities both within a single patient over time and between the patients. Habarou et al. (2017) suggested that patients with suspected disease of energy metabolism should undergo next-generation-based sequencing of genes in this pathway with subsequent confirmation by enzymatic analysis.

▼ Inheritance

The transmission pattern of NELABA in the families reported by Habarou et al. (2017) was consistent with autosomal recessive inheritance.

▼ Molecular Genetics

In 3 patients from 2 unrelated families with NELABA, Habarou et al. (2017) identified compound heterozygous missense mutations in the LIPT2 gene (617659.0001-617659.0003). All parents shared 1 mutation in common (L126R; 617659.0001). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Patient fibroblasts showed decreased lipoic acid-dependent enzymatic activities of the pyruvate dehydrogenase complex (PDHc), alpha-ketoglutarate dehydrogenase complex (KGDHc), and branched-chain ketoacid dehydrogenase complex (BCKDHc). Patient cells showed decreased or even absent lipoylation of protein compared to controls, which could be rescued by expression of wildtype LIPT2. Mitochondrial respiratory chain enzyme activities were normal, but patient cells showed decreased oxygen consumption and respiratory capacity compared to controls when challenged. Lip2-deficient yeast showed a growth defect that was unable to be rescued with lipoic acid, and patient fibroblasts treated with lipoic acid did not show improvement of the enzymatic defects. The findings indicated that LIPT2 mutations altered lipoate binding in the E2 subunits of alpha-oxoacid dehydrogenases, resulting in a severe clinical encephalopathy.

Tags: 11q13.4