Coming Soon - More symptoms with detailed explanation and theories for why develop as result of underlying mitochondrial disease.

Intro

This page provides an overview of symptoms experienced by a high percentage of FBXL4 children and demonstrates the multi-system vulnerability of the disease. Given the progressive nature of the disease, children can be expected to develop more symptoms with age. Every child is unique and no one single child will develop all of the following.

NOTE - Most "symptoms" are cross-disciplinary. For ease of recognition for readers with limited medical experience, each condition is assigned the most apparent system. I.e. Hyperventilation in FBXL4 is driven by the brain (nervous system), due to acid buildup from metabolism (all systems, listed here as endocrine), but because most people think lungs when they think hyperventilation, this condition is listed as Respiratory System.

Muscular System

• Low muscle mass

• Growth restriction / “Failure to Thrive”

• (Low muscle tone - See nervous system)

Skeletal System

Craniofacial

• Bossing forehead with supraorbital ridge protuberance (brow ridge)

• A broad nasal bridge and tip

• Smooth and long philtrum (space between the upper lip and nose)

• Up-slanting palpebral fissures - outside corners of the eyes that point upward

• Orofacial myofunctional disorders - including high arched roof of mouth palate

Other irregularities resulting from lack of proper loading of gravity (i.e. feet and legs if not regularly weight bearing)

Nervous System

Brain structural abnormalities

• Cerebral atrophy due to axon reduction (White matter hyperintensities)

• Underdeveloped cerebellum, basal ganglia, brain stem

These structural abnormalities lead to a variety of symptoms including:

• Low muscle tone

• Cerebral Palsy - A series of neurological disorders which affect ability to move, balance, and maintain posture

• Dysphagia (Difficulty sucking)

• Irregular sleep patterns

• Irregular eye movements (nystagmus, roving)

• Seizures

• Vision and/or hearing loss

• Autonomic storming

Cardiovascular System

• Tachycardia (increased heart rate) (due to nervous system abnormalities)

• Cardiomyopathy - Thickening of heart muscle

• Heart rhythm abnormalities (arrhythmias)

Respiratory System

• Rapid Breathing - Hyperventilation. May also be referred to as Tachypnea (rapid breathing, though generally shallow). 

  • In response to acid accumulation, the brain signals the lungs to initiate "Kussmaul Breathing". The intense breathing pattern helps the body expel extra carbon dioxide (CO2, an acid), which in turn raises the blood pH and compensates for the metabolic acidosis (build up of acid in the body due to metabolic condition).

  • FBXL4 children often breathe faster than normal children, but are especially labored when ill or any other event leads to more significant than normal metabolic distress. Note that FBXL4 children may initiate Kussmaul Breathing even when their blood pH is alkalotic. This is because the cerebral spinal fluid in the brain is frequently more acidic than the blood in FBXL4 (i.e. the brain is still acidic and so it continues to tell the rest of the body to respond).

• Increased risk for pneumonia (due to low tone throat protections)

Digestive System

• Increased gas

• Gastrointestinal dysmotility (Difficulty passing stools) (due to low muscle)

• Hepatopathy (Liver abnormalities)

Lymphatic System

• Neutropenia (low white blood cell count) - Immunodeficiency 

Integumentary System

• Hirsutism (excessive hair) including long eyelashes and thick eyebrows

Endocrine System

The primary impact of this disease is error of metabolism. These children are known to have chronic and episodic metabolic failure involving:

• High lactate (all FBXL children)

• High ammonia (many FBXL4 children)

To better understand FBXL4 disfunction on a cellular level, see Intro to Mitochondrial Processes.